The effect of bioenergetic impairment of cytosolic processes in spatio-temporal Ca²⁺ dynamics in a three-dimensional cardiomyocyte model

The heart consumes large amounts of energy with each beat. Mitochondria are the source of over 95% of this energy in the form of ATP and rely on increased Ca²⁺ uptake to stimulate production in times of increased work. Ca²⁺ uptake into the mitochondria primarily occurs within microdomains. Structural remodeling associated with heart failure may disrupt these microdomains leading to impaired mitochondrial Ca²⁺ uptake and energetic impairment. To investigate the effect of structural changes on single cell behavior, a model describing mitochondrial dynamics and energetics production is modified and incorporated into a recently developed three-dimensional model of spatio-temporal calcium handling, which preserves microdomain structure and incorporates stochastic processes in Ca²⁺ handling protein kinetics. Modifications to the mitochondria model included a reformulation of mitochondrial Ca²⁺ uniporter uptake, making it suitable for concentrations in microdomains. With this model we demonstrate the importance of an ordered structure within the cell for normal function. Changes in the arrangement of mitochondria can have a pronounced effect on intracellular Ca²⁺ dynamics through their energetic regulation of SERCA, leading to spatially heterogeneous sarcoplasmic reticulum uptake and loading

Thresholds for tracing ships' ballast water: An Australian case study

To limit the spread of non-indigenous marine species, ships can be legally required to conduct ballast water exchange (BWE) prior to discharging ballast water. It has been proposed to verify BWE by measuring concentrations of coastal tracers in ballast tanks, which should track their removal. Using 3 Australian ports as case studies (Port Botany, Port Curtis and Port Phillip Bay), each representing a different BWE verification difficulty level, the spatial and temporal variability of chromophoric dissolved organic matter (CDOM) and 3 trace elements (manganese [Mn], barium [Ba] and phosphorus [P]), were measured to assess their utility as tracers of coastal (unexchanged) ballast water. CDOM fluorescence at λex/λem = 320/414 nm (C2*) and 370/494 nm (C3*) and Mn concentrations were significantly higher in ports than in the adjacent Tasman Sea, except near port entrances and at a few sites in Port Botany. Ba concentrations demonstrated the least power to discriminate coastal sources, but P easily discriminated water from mesotrophic Port Phillip Bay. In general, tracers showed greater variation between and within ports, rather than between seasons. Conservative BWE thresholds were calculated to be 1.6 quinine sulphate equivalents for C2*, 0.9 quinine sulphate equivalents for C3*, 1.4 μg l-1 for Mn and 6.9 μg l -1 for Ba. Overall, these thresholds would allow water sourced from eastern Australian ports to be identified as coastal at 92%, 69% and 74% of sites examined using C3*, Mn and Ba, respectively, requiring 71 ± 26%, 54 ± 40% and 59 ± 38% replacement with mid-ocean water to be within ocean baseline concentration ranges. © Inter-Research 2010 · www.int-res.com

Analysis of preliminary phytochemical screening of Typhonium flagelliforme

Typhonium flagelliforme (Araceae) is a medicinal herb which is endowed with curative properties against a variety of illness including injuries, oedema, coughs, pulmonary ailments, bleeding and cancer. In order to assess its phytochemical components, an experiment was conducted on one to six month old ex vitro and in vitro extracts of T. flagelliforme. The active (ex vitro and in vitro) extracts of T. flagelliforme were screened for phytochemicals components such as alkaloids, flavonlids, terpenoids and steroids. Alkaloids and flavonoids are the main phytochemical constituents of T. flagelliformewhich are found to be in the highest amount in two and four month old of ex vitro plants. High amounts of main phytochemical constituents were observed during the flowering process which started in two month old plant and finished at the end of the three month old plant

In vitro mass propagation of Typhonium flagelliforme as affected by plant growth regulators

Tubers were used as explants in in vitro mass propagation of Rodent Tuber (Typhonium flagelliforme). The explants were obtained from sterile plantlets and placed in shoot induction medium containing basal salts of Murashige and Skoog (MS) and various concentrations of 6-benzylaminopurine (BAP) and -naphthaleneacetic acid (NAA). Treatment containing 5 mg/l (w/v) of BAP with 1 mg/l (w/v) of NAA produced the highest number of shoots per explant (29.17) after 12 weeks of culture and also the highest mean fresh weight of shoots formed in treatment containing 5 mg/l (w/v) of BAP with 1 mg/l (w/v) of NAA. For ex vitro establishment, well- rooted plantlets were transferred in potting medium containing peatmoss, perlite and vermiculite (3:1:1)

Sebaceous Carcinoma of the Eyelid

Sebaceous gland carcinoma of the eyelid is a very rare, slow growing tumor arising from the meibomian glands. In contrast to squamous cell carcinoma and basal cell carcinoma which arise frequently from the lower lid, sebaceous carcinoma arises from the upper lid where meibomian glands are more numerous. We present a case of sebaceous carcinoma in an elderly lady who presented with a slow growing tumor in the lateral third of the lower lid, without any lymph node metastasis. The tumor was treated by wide excision and the eyelid was reconstructed by Tenzel semilunar flap

Agreement between bioelectrical impedance and dual energy X-ray absorptiometry in assessing fat, lean and bone mass changes in adults after a lifestyle intervention

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Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension.

BACKGROUND: Coagulation factor VIII (FVIII) deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF), which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by RT-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab-reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 5 exons within the int22h-1 repeat responsible for intron 22 inversions in 40% of severe haemophiliacs. A reciprocal relationship between the presence of short isoforms and full-length FVIII transcript suggested potential splice-switching mechanisms. CONCLUSIONS/SIGNIFICANCE: The pulmonary endothelium is confirmed as a site of FVIII secretion, with evidence of synthesis, cell surface expression, and coexpression with vWF. There is complex alternate transcription initiation from the FVIII gene. These findings provide a framework for future research on the regulation and perturbation of FVIII synthesis, and of potential relevance to haemophilia, thromboses, and pulmonary hypertensive states

Familial congenital glaucoma and epilepsy: a case series.

We present two siblings from consanguineous marriage, both with congenital glaucoma and seizure disorders with progressive visual impairment and blindness. The pedigree showed that five (one male and four females) of the eleven siblings have varied degrees of visual impairment to blindness with seizure disorders. To the best of our knowledge, familial congenital glaucoma with epilepsy has not been reported, hence the communication to highlight this unusual condition which could be an association or syndromic.Key words: Consanguinity, Familial, Congenital glaucoma, Epilepsy

Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK

Rare earth elements (REEs) in the tropical South Atlantic and quantitative deconvolution of their non-conservative behavior

This study presents new concentration measurements of dissolved REEs (dREEs) along a full-depth east-west section across the tropical South Atlantic (~12°S), and uses these data to investigate the oceanic cycling of the REEs. Enrichment of dREEs, associated with the redox cycling of Fe-Mn oxides, is observed in the oxygen minimum zone (OMZ) off the African shelf. For deeper-waters, a multi-parameter mixing model was developed to deconvolve the relative importance of physical transport (i.e. water mass mixing) from biogeochemical controls on the dREE distribution in the deep Atlantic. This approach enables chemical processes involved in REE cycling, not apparent from the measurements alone, to be distinguished and quantified. Results show that the measured dREE concentrations below ~1000 m are dominantly controlled (>75%) by preformed REE concentrations resulting from water mass mixing. This result indicates that the linear correlation between dREEs and dissolved Si observed in Atlantic deep waters results from the dominantly conservative behaviour of these tracers, rather than from similar chemical processes influencing both dREEs and Si. Minor addition of dREEs (~10% of dNd and ~5% of dYb) is observed in the deep (>~4000 m) Brazil Basin, resulting from either remineralization of particles in-situ or along the flow path. Greater addition of dREEs (up to 25% for dNd and 20% for dYb) is found at ~1500 m and below ~4000 m in the Angola Basin near the African continental margin. Cerium anomalies suggest that different sources are responsible for these dREE addition plumes. The 1500 m excess is most likely attributed to dREE release from Fe oxides, whereas the 4000 m excess may be due to remineralization of calcite. Higher particulate fluxes and a more sluggish ocean circulation in the Angola Basin may explain why the dREE excesses in this basin are significantly higher than that observed in the Brazil Basin. Hydrothermal venting over the mid-Atlantic ridge acts as a regional net sink for light REEs, but has little influence on the net budget of heavy REEs. The combination of dense REE measurements with water mass deconvolution is shown to provide quantitative assessment of the relative roles of physical and biogeochemical processes in the oceanic cycling of REEs.X.-Y. Zheng was supported by the Clarendon Scholarship, the Exeter College Mandarin Scholarship from University of Oxford, the Chinese Student Awards from the Great Britain–China Educational Trust (GBCET) and W Wing Yip and Brothers bursaries.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.gca.2016.01.01